ID VRK2_MOUSE Reviewed; 503 AA. AC Q8BN21; Q3U415; Q5F1Z5; Q5SP88; Q8BPU8; Q8CJ46; Q91WS1; Q9CZF9; DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot. DT 10-OCT-2003, sequence version 2. DT 27-MAR-2024, entry version 173. DE RecName: Full=Serine/threonine-protein kinase VRK2; DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q86Y07}; DE AltName: Full=Vaccinia-related kinase 2; GN Name=Vrk2; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; RX PubMed=12417526; DOI=10.1093/hmg/11.24.3047; RA Agoulnik A.I., Lu B., Zhu Q., Truong C., Ty M.T., Arango N., Chada K.K., RA Bishop C.E.; RT "A novel gene, Pog, is necessary for primordial germ cell proliferation in RT the mouse and underlies the germ cell deficient mutation, gcd."; RL Hum. Mol. Genet. 11:3047-3053(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC STRAIN=C57BL/6J, and NOD; RC TISSUE=Dendritic cell, Embryo, Eye, and Spleen; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=12782311; DOI=10.1016/s0014-5793(03)00501-5; RA Vega F.M., Gonzalo P., Gaspar M.L., Lazo P.A.; RT "Expression of the VRK (vaccinia-related kinase) gene family of p53 RT regulators in murine hematopoietic development."; RL FEBS Lett. 544:176-180(2003). RN [6] RP FUNCTION, SUBCELLULAR LOCATION, AND AUTOPHOSPHORYLATION. RX PubMed=14645249; DOI=10.1074/jbc.m310813200; RA Nichols R.J., Traktman P.; RT "Characterization of three paralogous members of the Mammalian vaccinia RT related kinase family."; RL J. Biol. Chem. 279:7934-7946(2004). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=31142202; DOI=10.1080/19491034.2019.1618175; RA Cheng L.C., Baboo S., Lindsay C., Brusman L., Martinez-Bartolome S., RA Tapia O., Zhang X., Yates J.R. III, Gerace L.; RT "Identification of new transmembrane proteins concentrated at the nuclear RT envelope using organellar proteomics of mesenchymal cells."; RL Nucleus 10:126-143(2019). CC -!- FUNCTION: Serine/threonine kinase that regulates several signal CC transduction pathways (PubMed:14645249). Modulates the stress response CC to hypoxia and cytokines, such as interleukin-1 beta (IL1B) and this is CC dependent on its interaction with MAPK8IP1, which assembles mitogen- CC activated protein kinase (MAPK) complexes (By similarity). Inhibition CC of signal transmission mediated by the assembly of MAPK8IP1-MAPK CC complexes reduces JNK phosphorylation and JUN-dependent transcription CC (By similarity). Phosphorylates histone H3 (By similarity). CC Phosphorylates 'Thr-18' of p53/TP53, and thereby increases its CC stability and activity (By similarity). Phosphorylates BANF1 and CC disrupts its ability to bind DNA and reduces its binding to LEM domain- CC containing proteins (By similarity). Down-regulates the transactivation CC of transcription induced by ERBB2, HRAS, BRAF, and MEK1 (By CC similarity). Blocks the phosphorylation of ERK in response to ERBB2 and CC HRAS (By similarity). May also phosphorylate MAPK8IP1 (By similarity). CC Can also phosphorylate the following substrates that are commonly used CC to establish in vitro kinase activity: casein, MBP and histone H2B, but CC it is not sure that this is physiologically relevant (By similarity). CC {ECO:0000250|UniProtKB:Q86Y07, ECO:0000269|PubMed:14645249}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000250|UniProtKB:Q86Y07}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990; CC Evidence={ECO:0000250|UniProtKB:Q86Y07}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q86Y07}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609; CC Evidence={ECO:0000250|UniProtKB:Q86Y07}; CC -!- SUBUNIT: Interacts with MAP3K7, MAP2K7, MAP2K1, KSR1, RAN and MAPK8IP1. CC {ECO:0000250|UniProtKB:Q86Y07}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14645249}. CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:31142202}; Single- CC pass type IV membrane protein {ECO:0000255}. Mitochondrion membrane CC {ECO:0000250|UniProtKB:Q86Y07}; Single-pass type IV membrane protein CC {ECO:0000255}. Nucleus envelope {ECO:0000269|PubMed:31142202}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8BN21-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8BN21-2; Sequence=VSP_008543; CC Name=3; CC IsoId=Q8BN21-3; Sequence=VSP_008541, VSP_008542; CC -!- TISSUE SPECIFICITY: Expressed in liver, kidney and muscle. Weakly CC expressed in thymus, bone marrow and spleen. CC {ECO:0000269|PubMed:12782311}. CC -!- DEVELOPMENTAL STAGE: Weakly expressed in embryo compared to VRK1 and CC VRK3. Expressed from 10.5 dpc to 14 dpc in developing liver and then CC decreases. It increases again from 17.5 dpc and remains thereafter. CC Highly expressed in hematopoietic embryonic tissues from 10.5 dpc to CC 14.5 dpc. Weakly expressed in the yolk-sac. CC {ECO:0000269|PubMed:12782311}. CC -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:14645249}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr CC protein kinase family. VRK subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF513620; AAN64922.1; -; mRNA. DR EMBL; AK012664; BAB28393.1; -; mRNA. DR EMBL; AK053297; BAC35335.1; -; mRNA. DR EMBL; AK154485; BAE32620.1; -; mRNA. DR EMBL; AC083815; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL929272; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC013520; AAH13520.1; -; mRNA. DR CCDS; CCDS24486.1; -. [Q8BN21-1] DR RefSeq; NP_001239376.1; NM_001252447.1. [Q8BN21-2] DR RefSeq; NP_081536.2; NM_027260.3. [Q8BN21-1] DR RefSeq; XP_006514864.1; XM_006514801.3. [Q8BN21-1] DR AlphaFoldDB; Q8BN21; -. DR SMR; Q8BN21; -. DR BioGRID; 213758; 6. DR STRING; 10090.ENSMUSP00000077471; -. DR iPTMnet; Q8BN21; -. DR PhosphoSitePlus; Q8BN21; -. DR SwissPalm; Q8BN21; -. DR EPD; Q8BN21; -. DR jPOST; Q8BN21; -. DR MaxQB; Q8BN21; -. DR PaxDb; 10090-ENSMUSP00000077471; -. DR PeptideAtlas; Q8BN21; -. DR ProteomicsDB; 299732; -. [Q8BN21-1] DR ProteomicsDB; 299733; -. [Q8BN21-2] DR ProteomicsDB; 299734; -. [Q8BN21-3] DR Pumba; Q8BN21; -. DR Antibodypedia; 30474; 254 antibodies from 30 providers. DR DNASU; 69922; -. DR Ensembl; ENSMUST00000078362.13; ENSMUSP00000077471.7; ENSMUSG00000064090.15. [Q8BN21-1] DR Ensembl; ENSMUST00000109504.8; ENSMUSP00000105130.2; ENSMUSG00000064090.15. [Q8BN21-1] DR GeneID; 69922; -. DR KEGG; mmu:69922; -. DR UCSC; uc007igf.2; mouse. [Q8BN21-1] DR UCSC; uc007igg.2; mouse. [Q8BN21-3] DR UCSC; uc011xsk.2; mouse. [Q8BN21-2] DR AGR; MGI:1917172; -. DR CTD; 7444; -. DR MGI; MGI:1917172; Vrk2. DR VEuPathDB; HostDB:ENSMUSG00000064090; -. DR eggNOG; KOG1164; Eukaryota. DR GeneTree; ENSGT00940000158042; -. DR HOGENOM; CLU_019279_4_3_1; -. DR InParanoid; Q8BN21; -. DR OMA; RYCPSGN; -. DR OrthoDB; 4064676at2759; -. DR PhylomeDB; Q8BN21; -. DR TreeFam; TF106473; -. DR Reactome; R-MMU-2980766; Nuclear Envelope Breakdown. DR Reactome; R-MMU-2995383; Initiation of Nuclear Envelope (NE) Reformation. DR Reactome; R-MMU-9013149; RAC1 GTPase cycle. DR Reactome; R-MMU-9013404; RAC2 GTPase cycle. DR Reactome; R-MMU-9013405; RHOD GTPase cycle. DR Reactome; R-MMU-9013408; RHOG GTPase cycle. DR Reactome; R-MMU-9013423; RAC3 GTPase cycle. DR BioGRID-ORCS; 69922; 2 hits in 80 CRISPR screens. DR ChiTaRS; Vrk2; mouse. DR PRO; PR:Q8BN21; -. DR Proteomes; UP000000589; Chromosome 11. DR RNAct; Q8BN21; Protein. DR Bgee; ENSMUSG00000064090; Expressed in floor plate of midbrain and 199 other cell types or tissues. DR ExpressionAtlas; Q8BN21; baseline and differential. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB. DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI. DR GO; GO:0019901; F:protein kinase binding; ISO:MGI. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI. DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:2000659; P:regulation of interleukin-1-mediated signaling pathway; ISS:UniProtKB. DR GO; GO:0043408; P:regulation of MAPK cascade; ISS:UniProtKB. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR11909; CASEIN KINASE-RELATED; 1. DR PANTHER; PTHR11909:SF100; SERINE_THREONINE-PROTEIN KINASE VRK2; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q8BN21; MM. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Cytoplasm; Endoplasmic reticulum; KW Kinase; Membrane; Mitochondrion; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; KW Transferase; Transmembrane; Transmembrane helix. FT CHAIN 1..503 FT /note="Serine/threonine-protein kinase VRK2" FT /id="PRO_0000086807" FT TRANSMEM 482..502 FT /note="Helical; Anchor for type IV membrane protein" FT /evidence="ECO:0000255" FT DOMAIN 29..313 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 334..353 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 362..395 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 392..503 FT /note="Interaction with MAP3K7" FT /evidence="ECO:0000250|UniProtKB:Q86Y07" FT COMPBIAS 362..379 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 166 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 35..43 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 61 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 336 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q86Y07" FT VAR_SEQ 151..163 FT /note="LDVLEYIHENEYV -> VSLRDLTGDLLDI (in isoform 3)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_008541" FT VAR_SEQ 164..503 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_008542" FT VAR_SEQ 342..390 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_008543" FT CONFLICT 33 FT /note="K -> R (in Ref. 1; AAN64922)" FT /evidence="ECO:0000305" FT CONFLICT 226 FT /note="A -> P (in Ref. 2; BAB28393)" FT /evidence="ECO:0000305" FT CONFLICT 319 FT /note="P -> L (in Ref. 2; BAE32620 and 4; AAH13520)" FT /evidence="ECO:0000305" FT CONFLICT 333 FT /note="H -> R (in Ref. 2; BAE32620 and 4; AAH13520)" FT /evidence="ECO:0000305" SQ SEQUENCE 503 AA; 58119 MW; 6F29E3E412ECB221 CRC64; MAPRRKEKYK LPVPLPEGKI LDDMEGNRWA LGKMIGSGGF GLIYLAFPTN KPNKDARHVI KLEYQENGPL FSELKFYQRA AKRECIQKWI QQRKLDYLGI PVFYGFGLTD FKGRSYRFMV MERLGIDLQK LLDQNGGFKK LTVLQLGIRM LDVLEYIHEN EYVHGDIKAA NLLLDFTNPD RVYLADYGLS YRYCPNGNHK QYQEDPRKGH NGTIEFTSLD AHKGVAPSRR SDVEILGYCM LHWLFGKLPW EAKLDDPVAV QTAKTNLLDE LPESVLKWAP SGSSCSELVK YLMYVHNLAY DDKPDYQKLK KILNPDGVPL GPLEFSTKVQ SVHVRTPAQQ KVDSPKATRK PANEFPAKFP KKVHRETRAR QREEQEDSQP TMLQSRPAAP ENSRTRKIHE YSDIFSEMQS LQQTPSYMSF QGSYCKPYLD CTRRDPIRKP RSLPRYRHTP TGNLGVTDLE SSPRFWPAIF QLTLSEETKA DVYYYGITIF CLLIFVFLAL YFL //